Ketones borane-tetrahydrofuran

Enantioselective Ketone Reduction. Following Itsuno s lead for enantioselective reductions using diphenylvalinol, Kraatz was the first to describe the use of a 1 2 mixture of (5)-diphenylprolinol (1) and Borane-Tetrahydrofuran for the stoichiometric enantioselective reduction of ketone (2) to obtain the plant growth regulator triapenthenol (3) (eq 1). Although not characterized at the time, the species responsible for the enantiose-lectivity observed was presumed to be an oxazaborolidine-borane complex. ... 

Enantioselective Ketone Reduction. After the pioneering work of Itsuno et al., Corey s group isolated the 1,3,2-oxazaborolidine derived from chiral a,a-diphenyl-2-pyrrolidinemethanol (2) and applied it (and also other related B-alkyl compounds) to the stereoselective reduction of ketones with borane-tetrahydrofuran, borane-dimethyl sulfide (BMS) or catecholborane.It was named the CBS method (after Corey, Bakshi, and Shibata). Since then, the CBS method has become a standard and has been extensively used, specially for aromatic and a,p-unsaturated ketones, not only in academic laboratories but also in industrial processes. ... 

Asymmetric reduction of or y-functionalized alkyl aryl ketones provides a wide variety of chiral amino alcohols. Commercial -chloropropiophenone is reduced with borane-tetrahydrofuran adduct catalyzed by oxazaborolidine 45 to provide the chlorohydrin in over 99 % yield with 94 % ee. The resulting alcohol is a key intermediate for synthesis of the R form of fluoxetine (Prozac ), a serotonin-uptake inhibitor [53]. Using hydrogenation processes the functionalized amino ketones are converted directly into the respective products [8, 43e],... 

For the oxazaboroHdine-catalyzed reduction of prochiral ketones various borane reductants are employed. Borane-tetrahydrofuran and borane-dimethyl sulfide are the most frequently used reductants. Borane-l,4-thioxane [34], dibo-rane, catecholborane [35, 36, 37, 38], and diethylanihne-borane [39] are also useful borane reductants in this reduction system. 

High stereoselectivities (94-100 %) are attained in the reduction of aromatic ketones by use of a new chiral borane complex with (S)-2-amino-3-methyl-l,l-diphenylbutan-l-ol,(S-68) readily prepared in two steps from (S)-valine, in an experimentally convenient procedure961. (S)-Valine methyl ester hydrochloride was converted with excess of phenylmagnesium bromide into (S-68). The same treatment of (R)-valine gave (R-68). In a typical asymmetric reduction the reagent, prepared from (S-68) and borane, and the ketone (69) in tetrahydrofuran were kept at 30 °C for some hours. The corresponding alcohols were obtained in high optical purity. (S-68) could be recovered to more than 80% without racemization 96). 

Borane (as BH3 in tetrahydrofuran or dimethyl sulfide) is an even milder reducing agent than BH4G for the carbonyl group of aldehydes and ketones. This difference in reactivity can be used to advantage when selective reduction is necessary. For example, borohydride reduces a ketone carbonyl more rapidly than a carbon-carbon double bond, whereas borane reduces the carbon-carbon double bond more rapidly than carbonyl ... 

Another secondary borane useful for the conversion of alkenes into alcohols and of alkynes to aldehydes or ketones is catecholborane (1,3,2-benzodioxaborole), which is prepared from catechol and borane in tetrahydrofuran [1201] (equations 600 and 601). 

Procedure A. A solution of 100 mmoles of I -octene in 30 ml. of tetrahydrofurane was flushed with nitrogen and 33.3 ml. of a 1 M solution of borane in tetrahydrofurane was injected by hypodermic syringe to effect hydroboration. After 1 hr., 50 mmoles of methyl vinyl ketone in 15 ml. of tetrahydrofurane was added. After 2 hrs. at 40°, 15 ml. of water was added and the solution was heated at 40° for 1 hr. The solution was dried over magnesium sulfate for GLPC analysis ... 

Alpine-Borane is an effective, readily available reagent for the reduction of acetylenic ketones. This class of ketones is reduced somewhat slower than aldehydes but the reactions generally proceed at 25 °C. Straight chain alkyl acetylenic ketones are completely reduced after 8 hours at 25 °C using a 0.5 M solution of Alpine-Borane in tetrahydrofuran. More hindered internal acetylenic ketones may require 1 4 days under these conditions, but the process may be accelerated by performing the reaction in the absence of solvent. Acetylenic ketones are reduced faster than other ketones, and can also be reduced in the presence of a methyl ketone24. An example is the selective reduction of 7-nonyne-2,6-dione24. 

Pyridine-substituted nicotines, nornicotines, and anabasines are available from a-cyano-amines by a new synthesis. The syntheses of ( )-[l - N]nornicotine and ( )-[l - N]nicotine have been described, from cyclopropyl 3-pyridyl ketone and [ N]formamide. 4-Methylnicotine has been prepared it shows no nicotine-like pharmacological activity. " An investigation into the stereochemical factors involved in the behaviour of nicotine and related compounds in the Menschutkin reaction has been conducted.A bridged nicotine , 1,2,3,5,6,10b-hexahydropyrido[2,3-g]indolizine (44), has been synthesized by carboxylation of the dilithium derivative of 2-methylnornicotine followed by cyclisation and reduction with borane in tetrahydrofuran. Several 5-halogeno-nicotines have been prepared and their pK values and biological activities measured. ... 

Scheme 9.21. A representation of the reduction of phenylethanone (methyl phenyl ketone, acetophenone, CeHsCOCHa) to (f j-l-phenylethanol with borane (BH3) in oxacyclopentane (tetrahydrofuran, THF) with an (.S j-oxazaborohdine. (See Corey, E. J. Bakshi, R. K. Tetrahedron Lett., 1990, 611, and Rao, A. V. R. Guijar, M. K. Shamma, P. A. Kaiwar, V.

C6H5-C = CHC4Hg-n from a-diazoketones. Ethereal methyllithium added dropwise at 0 to a soln. of di-n-butyl-(l-phenyl-l-hexenyloxy)borane prepared from diazoacetophenone and tri-n-butylborane in tetrahydrofuran, the ice bath removed, stirred 1 hr. at room temp., methyl iodide added, and stirring continued 1.5 hrs. 2-hexyl phenyl ketone. Y 69%. Via vinyloxyboranes, a,a- and ,/5-dialkylated ketones can be obtained in good yield from a-diazoketones and methyl vinyl ketone respectively. F. e. s. D. J. Pasto and P. W. Wojtkowski, J. Org. Chem. 36, 1790 (1971). 

Molecular oxygen and a metalloporphyrin represent a potential catalytic system. Thus, it has been shown ° that [Rh (tetraphenylporphyrinato)Cl] is a very efficient catalyst for the reduction of a ketone to alcohol in the presence of oxygen and NaBH4 in tetrahydrofuran. The rate-determining step is reaction (8.6.1), in which the metalloporphyrin catalyst is formed, serving as a generator of borane (BH3), which can be then transferred to ketone (P = por-phyrinato) ... 

Sym. ketones. A soln. of cyclopentene in diglyme allowed to react with a soln. of borane in tetrahydrofuran, stirred 1 hr. at room temp., tetrahydrofuran removed by distillation under reduced pressure, water added, heated to 100°, flushed with GO, stirred, after 2.5 hrs. when GO-absorption has ceased ice-cooled and oxidized below 35° with HgOg/NaOH dicyclopentyl ketone. Y 90%. 

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